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Two chemosensory receptors together mediate carbon dioxide detection in Drosophila


Blood-feeding insects, including the malaria mosquito Anopheles gambiae, use highly specialized and sensitive olfactory systems to locate their hosts. This is accomplished by detecting and following plumes of volatile host emissions, which include carbon dioxide (CO2)1. CO2 is sensed by a population of olfactory sensory neurons in the maxillary palps of mosquitoes2,3 and in the antennae of the more genetically tractable fruitfly, Drosophila melanogaster4. The molecular identity of the chemosensory CO2 receptor, however, remains unknown. Here we report that CO2-responsive neurons in Drosophila co-express a pair of chemosensory receptors, Gr21a and Gr63a, at both larval and adult life stages. We identify mosquito homologues of Gr21a and Gr63a, GPRGR22 and GPRGR24, and show that these are co-expressed in A. gambiae maxillary palps. We show that Gr21a and Gr63a together are sufficient for olfactory CO2-chemosensation in Drosophila. Ectopic expression of Gr21a and Gr63a together confers CO2 sensitivity on CO2-insensitive olfactory neurons, but neither gustatory receptor alone has this function. Mutant flies lacking Gr63a lose both electrophysiological and behavioural responses to CO2. Knowledge of the molecular identity of the insect olfactory CO2 receptors may spur the development of novel mosquito control strategies designed to take advantage of this unique and critical olfactory pathway. This in turn could bolster the worldwide fight against malaria and other insect-borne diseases.

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Figure 1: Gr21a and Gr63a are co-expressed in the CO 2 -responsive chemosensory neurons.
Figure 2: Expression of both Gr21a and Gr63a confers CO 2 sensitivity on normally CO 2 -insensitive neurons.
Figure 3: Gr63a1 mutants are electrophysiologically and behaviourally insensitive to CO2.
Figure 4: Gr63a 1 mutants and the GAL4 and UAS controls are all indifferent to CO 2 in a T-maze, whereas wild-type and heterozygous Gr63a 1 flies show robust avoidance.


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We thank P. Howell and M. Q. Benedict of the CDC and MR4 for providing us with mosquitoes contributed by W. E. Collins; K. Kay and K. Fishilevich for technical assistance; and R. Axel, C. Bargmann, K. J. Lee and members of the Vosshall Laboratory for comments on the manuscript. This work was funded in part by a grant to R. Axel and L.B.V. from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative and by an NIH grant to L.B.V. Support was contributed to W.D.J. from an NIH MSTP grant, to P.C. from the Jane Coffin Childs Memorial Fund for Medical Research and to I.G.K. from the Human Frontier Science Program.

Author Contributions W.D.J. carried out all the experiments and analysed the data. P.C. and I.G.K. generated and characterized the Gr63a-sytRFP transgene in the laboratory of S. L. Zipursky at UCLA. W.D.J. and L.B.V. together designed the experiments, interpreted the results, produced the figures, and wrote the paper.

Genbank accession numbers for A. gambiae genes in this paper are: GPROR7 (AY843205), GPRGR22 (DQ989011) and GPRGR24 (DQ989013). Genbank accession numbers for D. melanogaster genes in this paper are: Gr10a (DQ989010), Gr21a (DQ989014) and Gr63a (DQ989012).

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Correspondence to Leslie B. Vosshall.

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Genbank accession numbers for A. gambiae genes in this paper are: GPROR7 (AY843205), GPRGR22 (DQ989011) and GPRGR24 (DQ989013). Genbank accession numbers for D. melanogaster genes in this paper are: Gr10a (DQ989010), Gr21a (DQ989014) and Gr63a (DQ989012). Reprints and permissions information is available at The authors declare no competing financial interests.

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Jones, W., Cayirlioglu, P., Grunwald Kadow, I. et al. Two chemosensory receptors together mediate carbon dioxide detection in Drosophila. Nature 445, 86–90 (2007).

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